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Der Pharma Chemica, 2012, 4(5):2029-2035

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ISSN 0975-413X
CODEN (USA): PCHHAX

A facile synthesis, characterization of N-substituted 7-methoxy-3-phenyl-4-

(3-piperizin-1-yl-propaxy) chromen-2-one
Devender Mandalaa, b, Sravanthi Chadaa, Umapathi Nallaa, Jalapathi Pochampallia*
a
Department of chemistry, PG College of Science, Osmania University, Hyderabad- 500004, India
b
Allied Fabrichem Pvt. Ltd, Plot No-185, Phase-II, IDA-Mallapur, Hyderabad-500076, India
______________________________________________________________________________
ABSTRACT

A series of novel N-substituted 7-methoxy-3-phenyl-4-(3-piperizin-1-yl-propaxy) chromen-2-one compounds have

been synthesized by reacting 7-methoxy-3-phenyl-4-(3- piperizin-1-yl-propaxy) chromen-2-one with various
substituted halo compounds in the presence of triethylamine/dichloromethane. The newly synthesized compounds
were purified and their structures were characterized by IR, 1H-NMR and Mass spectroscopy.

Key Words: Coumarins, 1, 3-Dibromopropane, Halo compounds, Piperizine.

______________________________________________________________________________
INTRODUCTION

The piperizines are a broad class of chemical compounds with several vital pharmalogical properties. These
compounds have been shown to potent analgesics, psychotolytic [1] and antifungal activities [2] [3]. N-substituted
piperizines have been reported to possess various activities like, local anesthetic, antihyperlipidemic, anticoagulant
[4] and also antihelmenthic, anticancer [5] [6] [7], antihistamic [8], antidepressant [9]. Some aryl piperizine
derivatives possess antienteroviral activity [10] [11], anti-HIV properties [12], Certain 1, 4-disubstituted aromatic
piperizines with extreme selectivity for the dopamine D4 receptor interact with a common micro domain [13] 1, 4-
disulfoally piperizines are used as buffering agents.

The incorporation of different halo substitutes in piperizine moiety is an significant synthetic strategy in medicinal
chemistry due to its wide range of biological applications, proper alkality, solubility nature in water and
physicochemical properties [14] [15]. General applications of these substituted piperizines including development of
different pharmaceutical intermediates, peptide analogues, antibiotics and other biologically active molecules for
different clinical drugs development [16] [17] [18].

Coumarins are wide spread in nature and also biological activities of different coumarins and its derivatives are
distinguished, they are anticoagulant, antimicrobial [19], anti-HIV, antioxidant [20], antiallergic, anticancer [21] and
antiviral activities [22]. A large number of structurally novel coumarins derivatives have ultimately been reported to
show substantial cytotoxicity and anti-HIV in vitro and in vivo [23] [24]. Several biological activities have been
reported in natural-occurring coumarins, from photo sensitizers to vasodilatation. Recently, the interest has been
given to synthetic derivatives of coumarins, such as fluorinated and 1-azo coumarins, which displayed moderate
analgesia properties and excellent anti-inflammatory. In this connection we report synthesis of new molecules which
contain piperizine and coumarin moieties within the framework.

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MATERIALS AND METHODS

Thin Layer Chromatography (TLC) was performed on E.Merk AL Silica gel 60 F254 plates and visualized under
UV light. The infrared (IR) spectra were determined in a perkin-Elmer Fourier transform (FDIR spectrum). 1H-
NMR spectra were recorded on Varian EM-360 (400MHz mercury plus) spectrometer in DMSO-d6 or CDCl3 and
calibrated using solvent signals [7.25(CDCl3) and 2.50(DMSO-d6)]. All chemical shifts recorded in (ppm) using
TMS as an internal standard. The mass spectra were recorded on Agilent ion trap MS. Spectrometer at energy of
ionizing electron equal to 70ev. Most of the reagents were purchased from Aldrich chemical company, Fluka and
Merck Company.

RESULTS AND DISCUSSION

Several N-substituted piperizine derivatives were synthesized by the reaction between 7-Methoxy-3-phenyl-4-(3-
piperzin-1-yl-propoxy)-chromen-2-one (5) and various substituted halo/other aromatic substituted compounds in
presence of a mild base (triethylamine) in dichloromethane as a solvent. The compound 4-(3-Bromo-propyl)-
piperazine-1-carbaxylic acid tert-butyl ester (2) was prepared by the reaction of Piperazine-1-carbaxylic acid tert-
butyl ester (1) with 1,3-dibromo propane using K2CO3-acetone to yielded 4-(3-Bromo-propyl)-piperazine-1-
carbaxylic acid tert-butyl ester (2) as white solid, the compound (2) alkylated with 4-Hydroxy-7-methoxy-3-phenyl-
chromen-2-one (3) [25] in presence of K2CO3 in acetonitrile to afford 4-[3-(7-Methoxy-2-oxo-3-phenyl-2H-
chromen-4-yloxy)-propyl]-piperazine-1-carboxylic acid tert-butyl ester (4). The compound (4) was deprotected with
TFA/DCM to afforded 7-Methoxy-3-phenyl-4-(3-piperzin-1-yl-propoxy)-chromen-2-one (5) a brown color solid.

Preparation of 4-(3-Bromo-propyl)-piperazine-1-carbaxylic acid tert-butyl ester (2):

Anhydrous potassium carbonate (5.55g, 40.32mmol) was added to a solution of Piperazine-1-carbaxylic acid tert-
butyl ester (1) (5.0g, 26.88mmol) in dry acetone followed by 1, 3-dibromo propane (3.27mL, 32.25mmol) at room
temperature. The reaction mixture stirred for 4h at same temperature and then the volatiles were evaporated under
reduced pressure, diluted with water and extracted with ethyl acetate (3x50mL). The combined organic layers dried
over Na2SO4 and evaporated by rotary to afford 7.20g (87.2%) of 4-(3-Bromo-propyl) - Piperazine-1-carbaxylic acid
tert-butyl ester (2) as off white color solid.
1
H-NMR-(400MHz) in CDCl3: 1.49 (s, 9H, -boc); 1.78 (m, 2H, -NCH2CH2CH2Br); 2.02 (t, 2H, -
NCH2CH2CH2Br); 2.38 (t, 4H, Piperazine); 3.46 (t, 4H, Piperazine); 3.82 (t, 2H, -NCH2); MS-m/z: 307 (M+H)+;
ESI-HRMS: m/z calcd. For C12H23BrN2O2 [M+H]+ 307.1390; Found: 307.1381.
Br

H
N O O O
(a) N O O O O O O (c)
(b)
+
N 87%,4h 78%,2h
N 87%,12h
O
O O OH O
O O N
N
(2) (3) HN (5)
(1) O N (4)
O

Reagents & Conditions:(a)1,3-dibromo propane,K2CO3-Acetone(b) Compound-(3), K2CO3,

ACN (c) TFA-CH2Cl2
Scheme-1

Preparation of 4-[3-(7-Methoxy-2-oxo-3-phenyl-2H-chromen-4-yloxy)-propyl]-piperazine-1-carboxylic acid

tert-butyl ester (4):
Potassium carbonate (3.3g, 24.42mmol) was added to a solution of 4-Hydroxy-7-methoxy-3-phenyl-chromen-2-one
(3) (4.3g, 16.28mmol) in acetonitrile (40mL) at room temperature. The mixture stirred for 30min, then added a
solution of 4-(3-Bromo-propyl)-piperazine-1-carbaxylic acid tert-butyl ester (2) (5.0g, 16.28mmol) in acetonitrile
(10mL). This mixture heated at 80C for 12h, cool to room temperature evaporated the solvent and dilute with
water, extracted with ethyl acetate (3x100mL) to get crude compound. The crude compound was purified by column
chromatography using neutral alumina. The pure compound elute at 1% methanol in chloroform as a mobile phase
to afford 11.2g (86.6%) of 4-[3-(7-Methoxy-2-oxo-3-phenyl-2H-chromen-4-yloxy)-propyl]-piperazine-1-carboxylic
acid tert-butyl ester (4) as a brown color solid.
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1
H-NMR-(400MHz) in CDCl3: 1.45 (s, 9H, -boc); 1.76-1.69 (m, 2H, -CH2- propyl); 2.25 (t, 4H, Piperazine);
2.38 (d, 2H, NCH2 propyl); 3.35 (t, 4H, Piperazine); 3.69 (t, 2H, OCH2 propyl); 3.94 (s, 3H, OCH3); 6.85 (s, 1H,
Ar-H); 6.88 (d, 1H, Ar-H); 7.47-7.34 (m, 5H, Ar-H); 7.75 (d, 1H, Ar-H); 13C-NMR in CDCl3 (75 MHz):
166.32, 163.76, 161.12, 156.76, 152.80, 133.65, 132.10, 130.43, 128.94, 114.87, 111.54, 108.98, 98.42, 80.43,
66.32, 58.64, 52.08, 51.19, 49.21, 29.34, 28.80; MS-m/z: 495 (M+H)+; ESI-HRMS: m/z calcd. For C28H34N2O6
[M+H] +495.2322; Found: 495.2301.

Preparation of 7-Methoxy-3-phenyl-4-(3-piperzin-1-yl-propoxy)-chromen-2-one (5):

To a solution of 4-[3-(7-Methoxy-2-oxo-3-phenyl-2H-chromen-4-yloxy)-propyl]-piperazine-1-carboxylic acid tert-
butyl ester (4) (10g, 20.24mmol) in DCM (5vol, 50mL) was added TFA (1vol, 10mL) at 0 C. The reaction mixture
was allowed to come to room temperature and stirred for 2 h. The solvent was evaporated under reduced pressure
and basified with saturated NaHCO3 solution, extracted with chloroform (3x100mL). the combined organic layers
dried over Na2SO4 evaporated by rotary to get 6.2g (78.4%) of 7-Methoxy-3-phenyl-4-(3-piperzin-1-yl-propoxy)-
chromen-2-one (5) as a brown color solid.
1
H-NMR-(400MHz) in CDCl3: 1.73-1.64 (m, 2H, -CH2- propyl); 2.28 (t, 2H, -NCH2 propyl); 2.42 (t, 4H,
Piperazine); 2.98 (t, 4H, Piperazine); 3.66 (t, 2H, -OCH2 propyl); 3.89 (s, 3H, -OCH3); 6.85 (s, 1H, Ar-H); 6.88
(d, 1H, Ar-H); 7.48-7.30 (m, 5H, Ar-H); 7.77 (d, 1H, Ar-H); 13C-NMR in CDCl3(75 MHz): 164.32, 154.86,
133.65, 132.10, 129.18, 124.94, 117.78, 77.50, 111.24, 72.43, 68.12, 56.75, 55.92, 54.26, 52.08, 50.12, 39.21, 28.86;
MS-m/z: 395 (M+H)+; ESI-HRMS: m/z calcd. For C23H26N2O4 [M+H] +: 395.1832; Found: 395.1821.

O O O O O O
R-x

O Et3N/CH2Cl2
O

N N

N N
H
R
(5)
(6a-6m)
Scheme-2

General procedure: Preparation of 7-Methoxy-3-phenyl-4-(3-piperzin-1-yl-propoxy)-chromen-2-one

derivatives (6a-6m):
Triethylamine (1.5eq) and corresponding halo compounds (1.1eq) was added to a solution of 7-Methoxy-3-phenyl-
4-(3-piperzin-1-yl-propoxy)-chromen-2-one (5) (1.0eq) in dichloromethane at 0C. Then the reaction mixture allow
to room temperature for 1-12h. After completion of the reaction, as indicated by TLC, The mixture was washed with
water and brine solution and extracted with dichloromethane. The organic layers dried over Na2SO4, evaporated by
rotary to afford corresponding products (6a-6m). All the products were confirmed by 1H-NMR, 13C-NMR, FT-IR,
HRMS and Mass spectral analysis.

Spectral data for compounds-(6a-6m):

7-Methoxy-4-[3-(4-methyl-piperzin-1-yl)-propoxy]-3-phenyl-chromen-2-one (6a), off white solid: 1H-NMR-
(400MHz) in CDCl3: 1.73-1.64 (m, 2H, -CH2- propyl); 2.16 (s, 3H, -NCH3); 2.28 (t, 2H, -NCH2 propyl); 2.42 (t,
4H, Piperazine); 2.98 (t, 4H, Piperazine); 3.76 (t, 2H, -OCH2- propyl); 3.92 (s, 3H, -OCH3); 6.95 (s, 1H, Ar-H);
6.98 (d, 1H, Ar-H); 7.42-7.32 (m, 5H, Ar-H);7.76 (d, 1H, Ar-H); 13C-NMR in CDCl3 (75 MHz): 166.43; 162.08,
159.86, 148.42, 132.10, 129.28, 127.18, 125.94, 117.78, 111.24, 109.18, 98.60, 77.50, 65.12, 57.57, 54.91, 50.12,
42.98, 29.26; MS-m/z: 407 (M-1)- -Ve Scan.

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Table 1: synthesis of N-alkyl derivatives of - 7-Methoxy-3-phenyl-4-(3-piperzin-1-yl-propoxy)-chromen-2-one (6a-6m)

Entries Reagents R= Product code Products Reaction Time % of yields

O
O O
1. CH3I 6a N N 2h. 90%

O O
2. Br 6b N N 4h. 78%

Br O O
3. 6c N N 3h. 96%
HO
OH
O

O O
Br O
4. 6d O N N 4h. 88%

O
O

O
O
O O O
O N N
5. 6e 12h. 87%
Cl O
O
O O

Br O O N
6. 6f N 1h. 98%

O
Br O O
7. 6g N N 1h 97%

O
OH O
8. 6h
O N N 12h 56%
OH
Cl
O

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O
O
S O O N
9. Cl Cl 6i N O 6h 73%
O S
O Cl
O

O
Cl
O O O
10. O 6j N N 4h. 78%

O
Br O
11. 6k O N N NO2 1h 98%
O2N
O

O
Br NO2
O O N
12. 6l N 2h 86%

NO2
O

O
Br O O
13. 6m
O N N O 4h. 96%
O O

7-Methaoxy-3-phenyl-4-[3-(4-propyl-piperazin-1-yl)-propoxy]-chromen-2-one (6b), off white solid: 1H-NMR-

(400MHz) in CDCl3: 0.90 (t, 3H, -CH3); 1.36-1.30 (m, 2H, -CH2CH3); 1.58-1.50 (m, 2H, -CH2 propyl); 1.98 (t,
2H, -NCH2); 2.38 (t, 4H, Piperazine); 2.67 (t, 4H, Piperazine); 2.88 (t, 2H, -NCH2); 3.83 (t, 2H, -OCH2 propyl);
3.93(s, 3H, -OCH3); 6.79 (s, 1H, Ar-H); 6.98 (d, 1H, Ar-H); 7.47-7.32 (m, 5H, Ar-H); 7.75 (d, 1H, Ar-H); 13C-
NMR in CDCl3 (75 MHz): 165.42; 163.56, 156.86, 146.12, 132.10, 131.08, 128.98, 126.24, 116.98, 110.43,
107.28, 101.10, 77.50, 65.12, 58.57, 52.61, 49.42, 38.92, 27.16, 22.65, 12.80; MS-m/z: 437 (M+H)+; ESI-HRMS:
m/z calcd. For C26H32N2O4 [M+H]+437.3226; Found: 437.3221.

4-{3-[4-(2-Hydroxy-ethyl)-piperazin-1-yl)-propoxy]-7-methaxy-3-phenyl-chromen-2-one(6c), thick liquid: 1H-

NMR-(400MHz) in CDCl3: 1.58-1.50 (m, 2H, -CH2 propyl); 1.98 (t, 2H, -NCH2 propyl); 2.38 (t, 4H, Piperazine);
2.68 (t, 4H, Piperazine); 2.90 (t, 2H, NCH2); 3.86 (t, 2H, -OCH2 propyl); 3.94 (q, 2H, -OCH2); 3.98 (s, 3H, -
OCH3); 6.79 (s, 1H, Ar-H); 6.98 (d, 1H, Ar-H); 7.37-7.28 (m, 5H, Ar-H); 7.72 (d, 1H, Ar-H); FT-IR in cm-1:
1054, 1171, 1456, 1742, 2925, 3435; MS-m/z: 439 (M+H)+; ESI-HRMS: m/z calcd. For C25H30N2O5 [M+H]
+
439.2433; Found: 439.2421.

7-Methoxy-3-phenyl-4-[3-(4-phenyl acetyl-piperzin-1-yl)-propoxy]-chromen-2-one (6d), black solid: 1H-NMR-

(400MHz) in CDCl3: 1.73-1.64 (m, 2H, -CH2 propyl); 2.28 (t, 2H, -NCH2); 2.42 (t, 4H, Piperazine); 2.98 (t, 4H,
Piperazine); 3.52 (s, 2H, -COCH2); 3.76 (t, 2H, -OCH2 propyl); 3.92 (s, 3H, -OCH3); 6.95 (s, 1H, Ar-H); 6.98 (d,
1H, Ar-H); 7.22-7.15 (m, 5H, Ar-H); 7.42-7.36 (m, 5H, Ar-H); 7.78 (d, 1H, Ar-H); 13C-NMR in CDCl3 (75 MHz):
168.34, 166.32, 162.89, 160.43, 152.26, 137.16, 132.98, 129.78, 127.50, 124.02, 112.78, 110.24, 106.56, 98.12,
68.90, 64.12, 56.26, 52.65, 49.76, 26.98; MS-m/z: 513 (M+H)+ +Ve Scan.

{4-[3-(7-Methoxy-2-oxo-3-phenyl-2H-chromen-4-yloxy)-propyl}-piperzin-1-yl}-oxo-acetic acid ethyl ester

(6e), colorless liquid: 1H-NMR-(400MHz) in CDCl3: 1.23 (t, 3H, -OCH2CH3); 1.72-1.66(m, 2H, -CH2 propyl);
2.32(m, 4H, Piperazine); 2.48 (t, 4H, Piperazine); 2.68 (t, 2H, -NCH2 propyl); 3.82 (t, 2H, -OCH2); 3.88 (s, 3H, -

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OCH3); 4.02 (q, 2H, -OCH2); 6.84 (s, 1H, Ar-H); 6.88 (d, 1H, Ar-H); 7.44-7.33 (m, 5H, Ar-H); 7.75 (d, 1H, Ar-
H); 13C-NMR in CDCl3 (75 MHz): 168.90, 163.22, 161.26, 159.56, 158.16, 152.78, 135.58, 129.08, 128.64,
126.58, 112.34, 109.44, 106.83, 98.10, 66.12, 60.02, 59.17, 56.78, 51.11, 49.42, 46.92, 28.65, 14.60; FT-IR in cm-1:
1055, 1450, 1665, 1728, 1742, 2925, 3035; MS-m/z: 495 (M+H)+; ESI-HRMS: m/z calcd. For C27H30N2O7
[M+H]+495.2033; Found: 495.2101.

4-[3-(4-allyl-piperazin-1-yl)-propoxy]-7-methoxy-3-phenyl-chromen-2-one (6f), thick liquid: 1H-NMR-

(400MHz) in CDCl3: 1.63-1.56 (m, 2H, -CH2 propyl); 1.78 (t, 4H, Piperazine); 2.37-2.31 (m, 4H, Piperazine);
3.06 (d, 2H, -CH2 allylic); 3.12 (t, 2H, -NCH2); 3.68 (t, 2H, -OCH2); 3.88 (s, 3H, -OCH3); 5.32 (dd, 2H, CH2
allylic); 5.96 (q, 1H, -CH allylic); 6.84 (d, 2H, Ar-H); 7.47-7.33 (m, 5H, Ar-H); 7.78 (d, 1H, Ar-H); 13C-NMR in
CDCl3 (75 MHz): 166.20, 158.76, 153.48, 146.65, 135.58, 132.85, 129.98, 128.64, 124.28, 118.78, 112.34,
111.94, 107.43, 96.80, 62.92, 57.28, 52.90, 47.42, 42.62, 26.87; MS-m/z: 435 (M+H)+; ESI-HRMS: m/z calcd. For
C26H32N2O4 [M+H]+435.5474; Found: 435.5461.

7-Methaoxy-3-phenyl-4-[3-(4-prop-2-ynyl-piperazin-1-yl)-propoxy]-chromen-2-one (6g), brown color solid: 1H-

NMR-(400MHz) in CDCl3: 1.52-1.45 (m, 2H, -CH2 propyl); 1.82 (t, 4H, Piperazine); 2.37-2.31 (m, 4H,
Piperazine); 2.54 (t, 2H, -NCH2 propyl); 3.36 (d, 2H, -NCH2 propargyl); 3.42 (s, 1H, -CH propargyl); 3.65 (t, 2H, -
OCH2 propyl); 3.88 (s, 3H, -OCH3); 6.84 (d, 2H, Ar-H); 7.47-7.33 (m, 5H, Ar-H); 7.78 (d, 1H, Ar-H); 13C-NMR
in CDCl3 (75 MHz): 165.60l, 161.90, 160.43, 151.26, 132.68, 128.87, 122.92, 114.15, 111.24, 107.56, 98.12,
78.78, 72.12, 64.67, 58.10, 54.16, 52.25, 45.86, 28.68; MS-m/z: 433 (M+H)+ +Ve Scan.

4-{3-[4-(3-Hydroxy-butyl)-piperazin-1-yl]-propoxy}-7-methoxy-3-phenyl-chromen-2-one(6h), color less liquid:

1
H-NMR-(400MHz) in CDCl3: 1.02 (d, 3H, -CH3 butanol); 1.52-1.45 (m, 2H, -CH2 propyl) 1.66 (q, 2H, -CH2
butanol); 2.44 (t, 4H, Piperazine); 2.54 (t, 4H, Piperazine); 2.66 (m, 4H, 2x NCH2 propyl and butanol); 3.68-3.62
(m, 1H, -CH butanol); 3.72 (t, 2H, -OCH2 propyl); 3.98 (s, 3H, -OCH3); 6.84 (d, 2H, Ar-H); 7.37-7.28 (m, 5H, Ar-
H); 7.72 (d, 1H, Ar-H); 13C-NMR in CDCl3(75 MHz): 25.60, 29.15, 38.88, 46.92, 48.22, 55.01, 58.48, 62.92,
66.12, 102.90, 107.86, 111.34, 113.38, 125.58, 127.74, 129.08, 136.38, 152.78, 160.66, 162.52, 166.80; FT-IR in
cm-1: 3415, 2910, 1725, 1463, 1150, 1055; MS-m/z: 465 (M-1)- -Ve Scan.

2-{4-[3-(7-Methoxy-2-oxo-3-phenyl-2H-chromen-4-yloxy)-propyl]-piperazin-1-yl}-ethanesulfonyl chloride(6i),
brown color solid: 1H-NMR-(400MHz) in DMSO-d6: 1.72-1.67 (m, 2H, -CH2 propyl), 2.34-2.27 (m, 4H,
Piperazine); 2.49-2.43 (m, 4H, Piperazine); 2.68 (t, 2H, -NCH2 propyl); 2.96 (t, 2H, -NCH2 Chloroethyl sulfonyl);
3.68 (t, 2H, -CH2 Chloroethyl sulfonyl); 3.76 (t, 2H, -OCH2 propyl); 3.88 (s, 3H, -OCH3); 6.84 (s, 1H, Ar-H); 6.88
(d, 1H, Ar-H); 7.44-7.33 (m, 5H, Ar-H); 7.75 (d, 1H, Ar-H); MS-m/z: 522 (M+H)++Ve Scan.

7-Methoxy-4-{3-[4-(4-methoxy-benzyl)-piperzin-1-yl]-propoxy}-3-phenyl-chromen-2-one (6j), white color

solid: 1H-NMR-(400MHz) in CDCl3: 1.73-1.64 (m, 2H, -CH2 propyl); 2.42 (t, 4H, Piperazine); 2.98 (t, 4H,
Piperazine); 3.02 (t, 2H, -NCH2 propyl); 3.70 (s, 2H, -NCH2Ar); 3.76 (t, 2H, -OCH2); 3.92 (s, 6H, 2x-OCH3); 6.95
(s, 1H, Ar-H); 6.96 (d, 3H, Ar-H); 7.12 (d, 2H, Ar-H); 7.42-7.36 (m, 5H, Ar-H); 7.78 (d, 1H, Ar-H); 13C-NMR in
CDCl3 (75 MHz): 167.20, 166.22, 161.76, 159.46, 152.78, 137.89, 132.58, 129.68, 127.64, 126.58, 117.89,
114.34, 110.34, 107.73, 97.90, 66.12, 59.17, 55.58, 52.31, 49.12, 26.55; MS-m/z: 515 (M+H)+; ESI-HRMS: m/z
calcd. For C38H34N2O5 [M+H] + 515.1421; Found: 515.1429.

7-Methoxy-4-{3-[4-(4-nitro-benzyl)-piperzin-1-yl]-propoxy}-3-phenyl-chromen-2-one (6k), pale yellow solid:

1
H-NMR-(400MHz) in CDCl3: 1.73-1.64 (m, 2H, -CH2 propyl); 2.42 (t, 4H, Piperazine); 2.98 (t, 4H,
Piperazine); 3.44 (t, 2H, -NCH2 propyl); 3.70 (s, 2H, -NCH2Ar); 3.76 (t, 2H, -OCH2 propyl); 3.92 (s, 3H, -OCH3);
6.95 (s, 1H, Ar-H); 6.98 (d, 1H, Ar-H); 7.12 (d, 2H, Ar-H); 7.42-7.36 (m, 5H, Ar-H); 7.78 (d, 1H, Ar-H); 8.22 (d,
2H, Ar-H); 13C-NMR in CDCl3 (75 MHz): 167.02, 163.76, 159.86, 152.78, 147.87, 142.24, 137.77, 135.58,
134.65, 129.08, 126.34, 124.28, 114.44, 110.44, 107.13, 96.80, 64.72, 58.17, 49.42, 40.92, 29.05; MS-m/z: 530
(M+H)+ +Ve Scan.

7-Methoxy-4-{3-[4-(3-nitro-benzyl)-piperzin-1-yl]-propoxy}-3-phenyl-chromen-2-one (6l), pale yellow solid:

1
H-NMR-(400MHz) in CDCl3: 1.72-1.66 (m, 2H, -CH2); 2.46 (t, 4H, Piperazine); 2.95 (t, 4H, Piperazine); 3.60
(t, 2H, -NCH2 propyl); 3.72 (s, 2H, -NCH2Ar); 3.76 (t, 2H, -OCH2 propyl); 3.92 (s, 3H, -CH3); 6.95 (s, 1H, Ar-H);
6.98 (d, 1H, Ar-H); 7.42-7.36 (m, 5H, Ar-H); 7.62 (d, 2H, Ar-H); 7.78 (d, 1H, Ar-H); 8.12 (d, 2H, Ar-H). MS-m/z:
530 (M+H) ++Ve Scan.

3-{4-[3-(7-Methoxy-2-oxo-3-phenyl-2H-chromen-4-yloxy)-propyl]-piperazin-1-yl}-propionic acid ethyl ester

(6m), brown color solid: 1H-NMR-(400MHz) in CDCl3: 1.23 (t, 3H, -OCH2CH3); 1.27 (t, 2H, -CH2 propyl); 1.72
(t, 2H, -COCH2); 2.34-2.27 (m, 5H, Piperazine, - NCH2); 2.49-2.43 (m, 5H, Piperazine, -NCH2); 2.68 (t, 2H, -
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Jalapathi Pochampalli et al Der Pharma Chemica, 2012, 4 (5):2029-2035
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NCH2CH2CO); 3.67 (t, 2H, -OCH2); 3.88 (s, 3H, -OCH3); 4.14 (q, 2H, -OCH2CH3); 6.84 (s, 1H, Ar-H); 6.88 (d,
1H, Ar-H); 7.12 (d, 5H, Ar-H); 7.75 (d, 1H, Ar-H); 13C-NMR in CDCl3 (75 MHz): 173.86, 168.87, 164.32,
158.86, 134.65, 132.10, 128.78, 125.34, 112.62, 110.64, 108.78, 100.90, 77.43, 61.01, 56.80, 55.08, 54.12, 32.50,
30.61, 27.20, 14.82; MS-m/z: 495 (M+H)+ +Ve Scan.

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